The combined contributions of the cue-familiarity and accessibility heuristics to feelings of knowing.
A model for the basis of feeling of knowing (FOK) is proposed, which combines 2 apparently competing accounts, cue familiarity (L. M. Reder, 1987), and accessibility (A. Koriat, 1993). Both cue familiarity and accessibility are assumed to contribute asynchronously to FOK, but whereas the effects of familiarity occur early, those of accessibility occur later and only when cue familiarity is sufficiently high to drive the interrogation of memory for potential answers. General information questions were used to orthogonally manipulate cue familiarity and accessibility. As expected, both familiarity and accessibility enhanced FOK judgments, but the effects of accessibility were found mostly when familiarity was high. This interactive pattern was replicated when FOK judgments were delayed but not when they were immediate. The results support the proposed cascaded model of FOK but also imply a differentiation between 2 variants of the accessibility heuristic.


Plant community dynamics, nutrient cycling, and alternative stable equilibria in peatlands.
Although observational data and experiments suggest that carbon flux and storage in peatlands are controlled by hydrology and/or nutrient availability, we lack a rigorous theory to account for the roles that different plant species or life-forms, particularly mosses, play in carbon and nutrient flux and storage and how they interact with different hydrologic sources of nutrients. We construct and analyze a model of peatlands that sheds some light on this problem. The model is a set of six coupled differential equations that define the flow of nutrients from moss and vascular plants to their litters, then to peat, and finally to an inorganic nutrient resource pool. We first analyze a simple version of this model (model 1) in which all nutrient input is from precipitation and enters the moss compartment directly, mimicking the dynamics of ombrotrophic bogs. There is a transcritical bifurcation that results in a switch of stability between two equilibrium bog communities: a moss monoculture and a community where mosses and vascular plants coexist. The bifurcation depends on the magnitudes of the input/output budget of the peatland and the life-history traits of the plants. We generalize model 1 to model 2 by dividing nutrient inputs between precipitation and groundwater, thus also allowing the development of minerotrophic fens that receive nutrient subsidies from both groundwater and precipitation and adding intraspecific competition (self-limitation) terms for both moss and vascular plants. Partitioning precipitation inputs between moss and the nutrient pool resulted in the greatest changes in model behavior, including the appearance of a lake and a vascular plant monoculture as well as the moss monoculture and coexistence equilibrium. As with model 1, these solutions are separated by transcritical bifurcations depending on critical combinations of parameters determining the input-output budget of the peatland as well as the life-history characteristics of the plant species. Model 2 also allowed for an early transient spike in vascular plant dominance followed by approach to near moss monoculture and then eventual approach to coexistence equilibrium. This generalized model mimics the broad features of successional development of peatlands from fens to bogs often found in the paleorecords of peat cores.


Coadministration of ketoconazole and cyclosporine for kidney transplant recipients: long-term follow-up and study of metabolic consequences.
In a prospective randomized study including 100 kidney transplant recipients, we previously reported on the safety and financial benefits of the coadministration of ketoconazole (keto) to cyclosporine (CsA)-treated kidney transplant recipients. In this study, we report on the long-term follow-up of these patients and their control group, as well as possible metabolic consequences of this drug combination. Evaluation of 51 keto-treated patients and their control group (49 patients) included graft function, lipogram, fasting blood glucose, liver function tests, serum calcium, phosphorus, and radiological and histopathologic assessments. Follow-up of these patients for 54 months showed that the CsA dose reduction was 72.9% at 12 months, decreased to 69.3% at the last follow-up. We also found that the mean keto dose required for CsA dose reduction decreased to 82.8 +/- 24.1 mg/d compared with the starting dose (100 mg/d). Diagnosis of acute rejection episodes was similar in both groups. However, in the control group, rejection episodes were more recurrent, with poorer response to treatment. Acute CsA nephrotoxicity was more common in the keto group, but this was encountered more at keto induction and was rapidly reversed on further reduction of CsA doses. Chronic graft dysfunction was statistically significantly less in the keto group during the first year. However, by the end of the study, the difference was not statistically significant. In this study, hepatotoxicity was similar in the two groups. On studying the metabolic consequences, we found that serum cholesterol, low-density lipoprotein, and triglyceride levels were lower in the keto group. Bone mineral contents in both groups were less than the mean values for age- and sex-matched healthy controls. From this study, we conclude that long-term use of low-dose keto in CsA-treated kidney transplant recipients is safe and cost-saving and may induce better graft function. Bone mineral contents, vitamin D blood levels, and lipid profiles are not affected by long-term keto coadministration in CsA-treated kidney transplant recipients.


Cobalt Ferrite Synthesized Using a Biogenic Sol-Gel Method for Biomedical Applications.
Cancer is one of the leading causes of death worldwide. Conventional treatments such as surgery, chemotherapy, and radiotherapy have limitations and severe side effects. Magnetic hyperthermia (MH) is an alternative method that can be used alone or in conjunction with chemotherapy or radiotherapy to treat cancer. Cobalt ferrite particles were synthesized using an innovative biogenic sol-gel method with powder of coconut water (PCW). The obtained powders were subjected to heat treatments between 500 °C and 1100 °C. Subsequently, they were characterized by thermal, structural, magnetic, and cytotoxic analyses to assess their suitability for MH applications. Through X-ray diffraction and Raman spectroscopy, it was possible to confirm the presence of the pure phase of CoFe2O4 in the sample treated at 1100 °C, exhibiting a saturation magnetization of 84 emu/g at 300 K and an average grain size of 542 nm. Furthermore, the sample treated at 1100 °C showed a specific absorption rate (SAR) of 3.91 W/g, and at concentrations equal to or below 5 mg/mL, is non-cytotoxic, being the most suitable for biomedical applications.


[Perioperative use of statins in vascular surgery].
The review is dedicated to studying the effect of perioperative use of statins while performing vascular operations, examining possible aftermaths of statins discontinuation in the perioperative period and discussing safety of perioperative use of statins. Cardiovascular complications constitute the most common cause of perioperative mortality while performing major noncardiac operations. Clinical studies demonstrated a favourable effect of statins on the cardiovascular complications rate in the perioperative period, therefore use of statins for prevention of cardiovascular diseases seems substantiated appropriate. Acting upon the levels of blood serum lipids, statins also influence various signal cellular pathways, exerting anti-inflammatory, antithrombotic and vasodilating effects. Thus, they may be used not only for patients with lipid metabolism impairments. However, currently required are further studies in order to determine optimal dosage, as well as the terms and duration of therapy with statins in the perioperative period.


Extensive transmission of SARS-CoV-2 BQ.1* variant in a population with high levels of hybrid immunity: A prevalence survey.
The SARS-CoV-2 BQ.1* variant rapidly spread globally in late 2022, posing a challenge due to its increased immune evasion. We conducted a prevalence survey in Brazil from November 16th to December 22nd, 2022, as part of a cohort study. We conducted interviews and collected nasal samples for RT-PCR testing and whole-genome sequencing. Cumulative incidence was estimated using RT-PCR positivity, cycle threshold values, and external data on the dynamics of RT-PCR positivity following infection. Among 535 participants, 54% had documented SARS-CoV-2 exposure before this outbreak and 74% had received COVID-19 vaccination. In this study, 14.8% tested positive for SARS-CoV-2, with BQ.1* identified in 90.7% of cases. Using case data and cycle threshold values, cumulative incidence was estimated at 56% (95%CI, 36-88%). Of the 79 positive participants, 48.1% had a symptomatic illness, with a lower proportion fulfilling the WHO COVID-19 case definition compared to prior Omicron waves. No participants required medical attention. Despite high population-level hybrid immunity, the BQ.1* variant attacked 56% of our population. Lower disease severity was associated with BQ.1* compared to prior Omicron variants. Hybrid immunity may provide protection against future SARS-CoV-2 variants but in this case was not able to prevent widespread transmission.


Striving for quality in advanced practice nursing education.
The issue of establishing and maintaining high-quality advanced practice educational programs, practice competencies, and certification criteria is currently the focus of much debate and discussion within nursing. This article focuses on the issue of accreditation for advanced practice nursing educational programs in four areas: (1) history of accreditation in nursing education; (2) accreditation of educational programs for clinical nurse specialists, nurse midwives, and nurse anesthetists; (3) accreditation of programs for nurse practitioners; and (4) current and future educational issues and challenges. To participate in shaping the changes occurring in the current health delivery system, the nursing profession and advanced practice nursing educators must present a strong, visionary, and collaborative voice concerning quality educational programs.


Ligustilide enhances pregnancy outcomes via improvement of endometrial receptivity and promotion of endometrial angiogenesis in rats.
Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels, which could promote focal angiogenesis to exert neuroprotection. However, there was no report that verified the exact effects of LIG on endometrial angiogenesis and the pregnancy outcomes. To explore the effects of LIG on low endometrial receptivity (LER) and angiogenesis, pregnancy rats were assigned into Control (saline treatment), LER (hydroxyurea-adrenaline treatment), LIG 20 mg/kg and LIG 40 mg/kg groups. Hematoxylin and eosin (H&E) staining was performed to evaluate endometrial morphology. Quantitative real-time PCR, immunofluorescence staining, western blot and immunohistochemistry staining were employed to assess the expression of endometrial receptivity factors and angiogenesis-related gene/protein, respectively. RNA sequencing was used to analyze the effects of LIG on LER caused by Kidney deficiency and blood stasis. We found that endometrial thickness and the implanted embryo number were substantially reduced in the hydroxyurea-adrenaline-treated pregnancy rats. At the same time, the gene and protein expressions of ERα, LIF, VEGFA and CD31 in the endometrium were markedly reduced, while the expressions of MUC1, E-cadherin were increased in the LER group. Administration of LIG raised the endometrial thickness and implanted embryos, as well as reversed the expressions of these factors. Collectively, our findings revealed that LIG could facilitate embryo implantation via recovery of the endometrium receptivity and promotion of endometrial angiogenesis.


Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex.
In Drosophila, the function of the Polycomb group genes (PcGs) and their target sequences (Polycomb response elements (PREs)) is to convey mitotic heritability of transcription programmes--in particular, gene silencing. As part of the mechanisms involved, PREs are thought to mediate this transcriptional memory function by building up higher-order structures in the nucleus. To address this question, we analysed in vivo the three-dimensional structure of the homeotic locus bithorax complex (BX-C) by combining chromosome conformation capture (3C) with fluorescent in situ hybridization (FISH) and FISH immunostaining (FISH-I) analysis. We found that, in the repressed state, all major elements that have been shown to bind PcG proteins, including PREs and core promoters, interact at a distance, giving rise to a topologically complex structure. We show that this structure is important for epigenetic silencing of the BX-C, as we find that major changes in higher-order structures must occur to stably maintain alternative transcription states, whereas histone modification and reduced levels of PcG proteins determine an epigenetic switch that is only partially heritable.


Role of elongation and secondary pathways in S6 amyloid fibril growth.
The concerted action of a large number of individual molecular level events in the formation and growth of fibrillar protein structures creates a significant challenge for differentiating between the relative contributions of different self-assembly steps to the overall kinetics of this process. The characterization of the individual steps is, however, an important requirement for achieving a quantitative understanding of this general phenomenon which underlies many crucial functional and pathological pathways in living systems. In this study, we have applied a kinetic modeling approach to interpret experimental data obtained for the aggregation of a selection of site-directed mutants of the protein S6 from Thermus thermophilus. By studying a range of concentrations of both the seed structures, used to initiate the reaction, and of the soluble monomer, which is consumed during the growth reaction, we are able to separate unambiguously secondary pathways from primary nucleation and fibril elongation. In particular, our results show that the characteristic autocatalytic nature of the growth process originates from secondary processes rather than primary nucleation events, and enables us to derive a scaling law which relates the initial seed concentration to the onset of the growth phase.


Oxidative destruction of DNA by the adriamycin-iron complex.
The 2:1 adriamycin-Fe(III) complex is able to bind to DNA and to catalyze its oxidative destruction. The binding of the drug-metal complex to DNA is indicated by characteristic spectral changes which are different from those seen with adriamycin intercalation and by the propensity of the drug-metal complex to precipitate DNA. Furthermore, intercalated adriamycin appears not to be available for iron binding. The resulting ternary complex is quite stable: it is not disrupted by incubation in the presence of EDTA and can be isolated by using Sephadex G-50 column chromatography. Disruption of the ternary complex requires vigorous conditions (extraction with phenol at 60 degrees C). The adriamycin-iron complex in free solution has the capacity to catalyze the reduction of oxygen by thiols. The DNA-bound drug-metal complex preserves this capacity over a wide range of complex/DNA ratios. As a consequence of this thiol-dependent oxygen reduction, DNA is cleaved. This thiol-dependent DNA cleavage has been shown to require hydrogen peroxide as an intermediate product. These results have led us to propose that the thiol-dependent DNA cleavage reaction has two stages involving (1) reduction of oxygen leading to hydrogen peroxide and then (2) peroxide-dependent DNA cleavage. An unusual property of this reaction is that the cleavage is not random but gives rise to a defined 2300 base pair fragment.


Risk of Pancreatic Cancer Among Individuals With Pathogenic Variants in the ATM Gene.
Pathogenic germline variants in the ATM gene have been associated with pancreatic cancer risk. Although genetic testing identifies these variants in approximately 1% to 3% of unselected patients with pancreatic cancer, the lifetime risk of pancreatic cancer among individuals with pathogenic ATM variants has not been well estimated. To estimate age-specific penetrance of pancreatic cancer in individuals with a pathogenic variant in the ATM gene. This was a multicenter cohort study of pancreatic cancer family registries in the US and Canada using pedigree data from 130 pancreatic cancer kindreds with a pathogenic germline ATM variant. Data analyses were performed from January 2020 to February 2021. Observational age-specific risk of pancreatic cancer. Penetrance was estimated using modified segregation analysis. The study population of 130 families (123 [95%] White families) comprised 2227 family members (mean age [SD], 58 [22] years; 1096 [49%] women) with complete records (ie, including familial relationships, pancreatic cancer diagnosis, ATM status, proband status, and age), of which 155 individuals had positive results for an ATM pathogenic variant, 16 had a negative result, and the remainder did not have a test result. In these 130 families, 217 individuals had pancreatic cancer: 78 families had 1 such member; 34 families had 2 such members; and 18 families had 3 or more members with pancreatic cancer. The average (range) age at diagnosis was 64 (31-98) years. The cumulative risk of pancreatic cancer among individuals with a germline pathogenic ATM variant was estimated to be 1.1% (95% CI, 0.8%-1.3%) by age 50 years; 6.3% (95% CI, 3.9%-8.7%) by age 70 years; and 9.5% (95% CI, 5.0%-14.0%) by age 80 years. Overall, the relative risk of pancreatic cancer was 6.5 (95% CI, 4.5-9.5) in ATM variant carriers compared with noncarriers. This multicenter cohort study found that individuals with a germline pathogenic ATM variant were at an increased lifetime risk of pancreatic cancer. These risk estimates can help guide decision-making when evaluating the risks and benefits of enhanced early detection surveillance.


Comparison of pure and mixed-type clear cell carcinoma of the ovary: a clinicopathological analysis of 341 Chinese patients.
This study aimed to analyze the clinicopathological features of pure and mixed-type ovarian clear cell carcinoma (CCC) in Chinese patients. Patients with ovarian CCC treated in our institution between 1982 and 2012 were identified by reviewing the database and medical charts. Patients were assigned into 2 groups based on histology (pure or mixed). Comparison of clinicopathological parameters was performed to determine the similarities and/or differences between pure and mixed CCC. Kaplan-Meier model was used in survival analysis. Of 341 patients with ovarian CCC, 46 (13.5%) mixed tumors were identified, and the most common combination was clear cell/endometrioid, accounting for 56.5%. Patients with mixed-type CCC tended to have higher level of serum cancer antigen 125 (P = 0.023) and advanced tumor stage (P = 0.001). No difference was observed in other features including age, tumor size, residual disease, lymph node metastasis, and coexisting endometriosis. Tumor recurrence occurred in 47.8% and 58.1% in patients with pure and mixed histology, respectively (P = 0.209). Two groups had comparable platinum-sensitive disease (42.1% in pure and 44.0% in mixed type, P = 0.860). Patients with pure CCC had an improved median survival (105 vs 56 months), although statistical significance was not achieved. Histology subclassification of mixed tumor revealed that patients with clear cell/endometrioid histology had better survival outcome than those with clear cell/serous type (median survival, 140 vs 43 months, P = 0.004; median progression-free survival, 49 vs 12 months, P = 0.001). Patients with mixed CCC tended to have elevated serum cancer antigen 125 and advanced tumor stage. However, no significant difference was observed between the pure and mixed tumors regarding prognosis.


Parity & untreated dental caries in US women.
While parity (number of children) reportedly is related to tooth loss, the relationship between parity and dental caries has not been extensively investigated. We used path analysis to test a theoretical model that specified that parity influences dental caries levels through dental care, psycho- social factors, and dental health damaging behaviors in 2635 women selected from the NHANES III dataset. We found that while increased parity was not associated with a greater level of total caries (DFS), parity was related to untreated dental caries (DS). The mechanisms by which parity is related to caries, however, remain undefined. Further investigation is warranted to determine if disparities in dental caries among women are due to differences in parity and the likely changes that parallel these reproductive choices.


Transcription of the glnB and glnA genes in the photosynthetic bacterium Rhodospirillum rubrum.
The PII protein, encoded by glnB, has a central role in the control of nitrogen metabolism in nitrogen-fixing prokaryotes. The glnB gene of Rhodospirillum rubrum was isolated and sequenced. The deduced amino acid sequence had very high sequence identity to other PII proteins. The glnA gene, encoding glutamine synthetase, was located 135 bp downstream of glnB and was partially sequenced. glnB is cotranscribed with glnA from a promoter with high similarity to the sigma 54-dependent promoter consensus sequence. A putative sigma 70 promoter was also identified further upstream of glnB. Northern blotting analyses showed that in addition glnA is either transcribed from an unidentified promoter or, more likely, that the glnBA transcript is processed to give the glnA mRNA. The total level of the two transcripts was much higher in nitrogen-fixing cells than in ammonia-grown cells.


Reproductive isolation among allopatric Drosophila montana populations.
An outstanding goal in speciation research is to trace the mode and tempo of the evolution of barriers to gene flow. Such research benefits from studying incipient speciation, in which speciation between populations has not yet occurred, but where multiple potential mechanisms of reproductive isolation (RI: i.e., premating, postmating-prezygotic (PMPZ), and postzygotic barriers) may act. We used such a system to investigate these barriers among allopatric populations of Drosophila montana. In all heteropopulation crosses we found premating (sexual) isolation, which was either symmetric or asymmetric depending on the population pair compared. Postmating isolation was particularly strong in crosses involving males from one of the study populations, and while sperm were successfully transferred, stored, and motile, we experimentally demonstrated that the majority of eggs produced were unfertilized. Thus, we identified the nature of a PMPZ incompatibility. There was no evidence of intrinsic postzygotic effects. Measures of absolute and relative strengths of pre- and postmating barriers showed that populations differed in the mode and magnitude of RI barriers. Our results indicate that incipient RI among populations can be driven by different contributions of both premating and PMPZ barriers occurring between different population pairs and without the evolution of postzygotic barriers.


Association between placenta previa and risk of hypertensive disorders of pregnancy: a meta-analysis based on 7 cohort studies.
The aim of this research is to evaluate the association between placenta previa and hypertensive disorders of pregnancy (HDP). A computerized literature search was carried out on PubMed to collect relevant articles on the association between placenta previa and HDP before November 2013. Pooled relative risk (RR) and 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 7 cohort studies were identified according to the inclusion criteria. Overall, a significantly inverse correlation between placenta previa and HDP was found when all study results were pooled into the meta-analysis (RR = 0.55, 95% CI: 0.32-0.97). For subgroup analyses, the same results were found in pregnancy-induced hypertension (PIH) group (RR = 0.36, 95% CI: 0.23-0.57) but not in other HDPs group (RR = 0.94, 95% CI: 0.44-2.00). This meta-analysis suggested a reduced risk for PIH in women with placenta previa.


Update on nonantibiotic therapies for acute gastroenteritis.
The aim of this review is to provide an update of nonantibiotic therapies for acute gastroenteritis (AGE), focusing on antiemetics and probiotics. The mainstay of therapy for nonsevere AGE remains oral rehydration therapy (ORT). Recent randomized controlled trials and metaanalyses have further strengthened the evidence-base supporting single-dose ondansetron administration in emergency departments to facilitate ORT based on evidence that it safely reduces intravenous fluid administration and hospitalization rates. Intravenous ondansetron administration and multiple-dose use should be avoided. A bimodal release ondansetron formulation was shown to improve outcomes in adolescents and adults with AGE in one study, but further evidence is required to support use. Recent large trials evaluating probiotic administration demonstrated a lack of benefit and guidelines that recommend their use should reevaluate their positions in light of this evidence. Furthermore, caution should be exercised when use is considered in high-risk populations and settings. The benefits, dosing/route, and target populations most likely to benefit from ondansetron have been further clarified. Optimization of the real-life effectiveness of this therapy will require implementation strategies. Recent high-quality evidence showing a lack of efficacy and potential harm associated with probiotic use suggests that routine use for AGE should be discouraged.


Nonsteroidal anti-inflammatory drug sulindac sulfide suppresses structural protein Nesprin-2 expression in colorectal cancer cells.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known for treating inflammatory disease and have been reported to have anti-tumorigenic effects. Their mechanisms are not fully understood, but both cyclooxygenase (COX) dependent and independent pathways are involved. Our goal was to shed further light on COX-independent activity. Human colorectal cancer cells were observed under differential interference contrast microscopy (DICM), fluorescent microscopy, and micro-impedance measurement. Microarray analysis was performed using HCT-116 cells treated with sulindac sulfide (SS). PCR and Western blots were performed to confirm the microarray data and immunohistochemistry was performed to screen for Nesprin-2 expression. Micro-impedance was repeating including Nesprin-2 knock-down by siRNA. HCT-116 cells treated with SS showed dramatic morphological changes under DICM and fluorescent microscopy, as well as weakened cellular adhesion as measured by micro-impedance. Nesprin-2 was selected from two independent microarrays, based on its novelty in relation to cancer and its role in cell organization. SS diminished Nesprin-2 mRNA expression as assessed by reverse transcriptase and real time PCR. Various other NSAIDs were also tested and demonstrated that inhibition of Nesprin-2 mRNA was not unique to SS. Additionally, immunohistochemistry showed higher levels of Nesprin-2 in many tumors in comparison with normal tissues. Further micro-impedance experiments on cells with reduced Nesprin-2 expression showed a proportional loss of cellular adhesion. Nesprin-2 is down-regulated by NSAIDs and highly expressed in many cancers. Our data suggest that Nesprin-2 may be a potential novel oncogene in human cancer cells and NSAIDs could decrease its expression.


Serum pro prostate specific antigen improves cancer detection compared to free and complexed prostate specific antigen in men with prostate specific antigen 2 to 4 ng/ml.
Pro prostate specific antigen (pPSA) is a precursor form of PSA enriched in tumor compared to benign prostate tissues that may be a more specific serum marker for prostate cancer. Serum pPSA was measured in the clinically relevant early detection PSA range of 2 to 10 ng/ml. Research use immunoassays were used to measure native and truncated forms of pPSA. The subject cohort contained 1,091 serum specimens from men enrolled in prostate cancer screening studies at 2 sites who had undergone prostate biopsy and were divided into PSA ranges of 2 to 4 ng/ml (benign 320, cancer 235) and 4 to 10 ng/ml (benign 315, cancer 221). In PSA ranges 2 to 4, 2 to 6, 4 to 10 and 2 to 10 ng/ml, pPSA in a ratio with free PSA (%pPSA) gave the highest cancer specificity. At 2 to 4 ng/ml and 90% sensitivity, %pPSA spared 19% of unnecessary biopsies compared to 10% for free PSA and 11% for complexed PSA(p <0.001). Similar results were obtained at PSA 2 to 6 ng/ml. At 90% sensitivity in the PSA 4 to 10 ng/ml range, %pPSA spared 31% of unnecessary biopsies compared to 20% for % free PSA and 19% for complexed PSA (p <0.0001). In the combined 2 to 10 ng/ml range, %pPSA spared 21% of unnecessary biopsies compared to 13% for % free PSA and 9% for complexed PSA (p <0.0001). The %pPSA significantly improved specificity for cancer detection and decreased the number of unnecessary biopsies in the PSA 2 to 4 ng/ml range. This relative improvement of %pPSA compared to % free PSA and complexed PSA was maintained throughout the PSA range of 2 to 10 ng/ml.


[Rate of ribosome movement along messenger RNA in E. coli under normal and inhibited translation].
Considerable decrease of polysome number (22% as compared with 48% in normally grown culture) was observed under methionine starvation of E. coli Hfr (Met-)culture . At the same time the amount of 70S ribosomes increased up to 32%, while it was 2--6% in the control, the content of free ribosome subunits (50S+30S) being stable. The number of polysomes was the same (congruent to 50%) both in the control culture and under inhibition of protein synthesis in E. coli Hfr(Met-) cells with chloramphenicol, the content of 70S ribosomes was increased (30%) like in the case of methionine starvation, and the amount of free ribosome subunits was decreased (24% as compared with 46% in the control). The rate of ribosome movement in polysomes in the presence of chloramphenicol is comparable with that in the control. The rate of ribosome movement along mRNA under methionine starvation in 1.6 times lower than in normally grown E.coli culture. The level of (14)C-leucine incorporation into newly synthesizing polysome proteins under chloramphenicol inhibition of protein synthesis and methionine starvation comprised 20% and 12% of the incorporation level inthe control respectively. It suggested that ribosomes under inhibition of protein synthesis by chloramphenicol or amino acid starvation continue their movement along mRNA with the rate comparable with that in the control. However in this case no peptide bonds are formed ("abortive" translocation).


Physicochemical characterization of creatine N-methylguanidinium salts.
Creatine is widely used as a dietary supplement for body builders to enhance athletic performance. As the monohydrate, its low solubility in water and high dose lead to water retention and gastrointestinal discomfort. Hence, alternative creatine derivatives with enhanced water solubility and potential therapeutic advantages have been synthesized. As a zwitterionic compound, creatine can form salts at the N-methyl guanidinium or carboxylic acid functional groups. In this study, we determined the aqueous solubilities and partition coefficients of six N-methyl guanidinium salts of creatine compared to those of creatine monohydrate; two of these were new salts, namely, creatine mesylate and creatine hydrogen maleate. The aqueous solubilities of the salts were significantly more than that of creatine monohydrate with the hydrochloride and mesylate being 38 and 30 times more soluble, respectively. The partition coefficients of the creatine salts were very low indicating their relatively high polarity. Permeabilities of creatine pyruvate, citrate, and hydrochloride in Caco-2 monolayers were compared to that of creatine monohydrate. Aside from the creatine citrate salt form that had reduced permeability, there were no significant differences in permeability characteristics in Caco-2 monolayers. Typical of an amphoteric compound, creatine is least soluble in the pH region near the isoelectric point.


A randomized controlled trial of a 'buddy' programme to improve children's attitudes toward the disabled.
Children's attitudes to their disabled peers exert a powerful influence on the process of integration of the disabled. This study reports a randomized controlled trial of a 'buddy' interaction programme in which gender-matched able-bodied and disabled schoolmates were paired over a three-month period. 43 per cent of the buddy children had a significant improvement in attitudes, compared with 18 per cent of the controls. Buddies also got to know significantly more disabled schoolmates than did the control children. There was a secondary effect on parents, with both fathers and mothers of buddy children having significant improvements in attitude. The implications of these results for the social success of disabled children are discussed.


Reverse shoulder arthroplasty in patients with pre-operative impairment of the deltoid muscle.
The indications for reverse shoulder arthroplasty (RSA) continue to be expanded. Associated impairment of the deltoid muscle has been considered a contraindication to its use, as function of the RSA depends on the deltoid and impairment of the deltoid may increase the risk of dislocation. The aim of this retrospective study was to determine the functional outcome and risk of dislocation following the use of an RSA in patients with impaired deltoid function. Between 1999 and 2010, 49 patients (49 shoulders) with impairment of the deltoid underwent RSA and were reviewed at a mean of 38 months (12 to 142) post-operatively. There were nine post-operative complications (18%), including two dislocations. The mean forward elevation improved from 50° (sd 38; 0° to 150°) pre-operatively to 121° (sd 40; 0° to 170°) at final follow-up (p < 0.001). The mean Constant score improved from 24 (sd 12; 2 to 51) to 58 (sd 17; 16 to 83) (p < 0.001). The mean Single Assessment Numeric Evaluation score was 71 (sd 17; 10 to 95) and the rate of patient satisfaction was 98% (48 of 49) at final follow-up. These results suggest that pre-operative deltoid impairment, in certain circumstances, is not an absolute contraindication to RSA. This form of treatment can yield reliable improvement in function without excessive risk of post-operative dislocation.


Nano-to-meso structure of cellulose nanocrystal phases in ethylene-glycol-water mixtures.
The self-assembly and phase behavior of cellulose nanocrystals (CNCs) in binary liquid mixtures of ethylene-glycol (EG):water was investigated. Our findings indicate that a small fraction of water delays the onset of colloidal jammed states previously reported in water-free organic solvents. Here the full phase diagram of CNCs evolves, including the chiral nematic phase (N*), characterized by long-range orientational order and non-isotropic macroscopic properties. Furthermore, the effect of the solvent-mixture composition on the properties of the CNC mesophases is found to be scale-dependent: the micron-size pitch of the N* phase decreases as the dielectric constant (εr) of the solvent mixture is reduced (higher EG content). Yet the nanometric inter-particle spacing of the CNC rods (measured using SAXS and cryo-TEM) is almost independent on the EG content. Also, unlike theoretical predictions, the transition to the biphasic regime is not sensitive to εr of the solvent mixtures and takes place at a higher CNC volume fraction than in aqueous suspensions. These observations may be rationalized by hypothesizing that vicinal water, adsorbed at the CNC surface, prevents kinetic arrest, and dictates the local dielectric constant and thus the effective diameter of the rods (via the Debye length), while εr of the liquid-mixture dominates the pitch length (micron scale) and the optical properties. These findings indicate that the water content of EG:water mixtures may be used for engineering colloidal inks where delayed kinetic arrest and jamming of the CNCs enable printing and casting of tunable, optically-active thin films and coatings.


Targeted over-expression of glutamate transporter 1 (GLT-1) reduces ischemic brain injury in a rat model of stroke.
Following the onset of an ischemic brain injury, the excitatory neurotransmitter glutamate is released. The excitotoxic effects of glutamate are a major contributor to the pathogenesis of a stroke. The aim of this study was to examine if overexpression of a glutamate transporter (GLT-1) reduces ischemic brain injury in a rat model of stroke. We generated an adeno-associated viral (AAV) vector expressing the rat GLT-1 cDNA (AAV-GLT1). Functional expression of AAV-GLT1 was confirmed by increased glutamate clearance rate in non-stroke rat brain as measured by in vivo amperometry. AAV-GLT1 was injected into future cortical region of infarction 3 weeks prior to 60 min middle cerebral artery occlusion (MCAo). Tissue damage was assessed at one and two days after MCAo using TUNEL and TTC staining, respectively. Behavioral testing was performed at 2, 8 and 14 days post-stroke. Animals receiving AAV-GLT1, compared to AAV-GFP, showed significant decreases in the duration and magnitude of extracellular glutamate, measured by microdialysis, during the 60 minute MCAo. A significant reduction in brain infarction and DNA fragmentation was observed in the region of AAV-GLT1 injection. Animals that received AAV-GLT1 showed significant improvement in behavioral recovery following stroke compared to the AAV-GFP group. We demonstrate that focal overexpression of the glutamate transporter, GLT-1, significantly reduces ischemia-induced glutamate overflow, decreases cell death and improves behavioral recovery. These data further support the role of glutamate in the pathogenesis of ischemic damage in brain and demonstrate that targeted gene delivery to decrease the ischemia-induced glutamate overflow reduces the cellular and behavioral deficits caused by stroke.


Age and gender differences in hip extension and flexion torque steadiness.
Lower extremity torque steadiness has been shown to be an independent predictor of functional performance in older women. Hip muscle function is crucial for many types of activities of daily living, yet existing studies investigating torque steadiness for lower extremities are limited to assessing steadiness at the knee and ankle. The purpose of this study was to compare age and gender differences in hip extension (HE) and flexion (HF) strength, torque steadiness, and torque accuracy (TA). Twenty young adults (10 men, 10 women; age 24.0 ± 2.2 years) and 21 older adults (11 men, 10 women; age 65.4 ± 4.5 years) matched across age for height and body mass participated. Dominant leg HE and HF isometric strength was assessed by maximal voluntary contractions (MVC); relative (5, 25 and 50% MVC) and absolute (25 Nm) torque steadiness were assessed as standard deviation and coefficient of variation of torque fluctuations, and TA was determined as the mean deviation from target torque levels. MVC was lower for HF than HE (p = 0.007), but HE had greater torque fluctuations (p < 0.05). For HE, the coefficient of variation of 5% MVC was greater for older than young adults (p < 0.05) and greater for women than men (p < 0.05). For HF torque steadiness there were no age or gender differences (p > 0.05). For both HE and HF, older adults were less accurate (higher TA) than their young counterparts at 25 Nm (p < 0.022). Our results indicate older as compared to young adults, and women as compared to men are less steady (greater torque fluctuations) in HE at 5% MVC target torque levels, but not at higher torque levels. For HF, torque steadiness is similar across low to high target torque levels in both genders and across younger and older adults. For both HE and HF, TA is impaired in older compared to young adults at absolute target torque levels, but not at relative torque levels.


Developing sustainable land-use patterns at watershed scale using nexus of soil, water, energy, and food.
Aside from the many services that soil provides, it also stores water and makes it available to crops, which is critical for food security. However, the necessity of further studies for overcoming the existing gap in relation to the role of soil in the water, energy, and food nexus system has been preoccupying the experts and specialists around the world for some time. In this sense, the balance between many key ecosystem components based on the Soil, water, energy, and food (SWEF) nexus framework is one of the key characteristics of holistic and accommodative watershed management systems. To the best of our knowledge, the watershed scale is used as a planning unit for the first time in the current study to construct a conceptual model for adaptive management of optimum land-use/cover allocation using SWEF. The method was then used for the Shazand Watershed, Iran. Numerous metrics, such as soil erosion, soil organic carbon (SOC), water and energy use, mass efficiency, and economic efficiency, were investigated. Finally, a compound indicator was used to generate the SWEF nexus index (SWEFNI) for various land-uses/crops for the node year 2014. SWFENI ranged from 0.19 (worst) for rangeland to 0.78 (best) for almond plantations, according to the findings. The study's present approach may be tested worldwide.


Telomere length variation in biliary tract metaplasia, dysplasia, and carcinoma.
Biliary tract carcinoma, including carcinoma of the gallbladder, intrahepatic bile ducts (cholangiocarcinoma), and extrahepatic bile ducts, affects 7500 people in the United States annually, and has an overall 32% 5-year survival rate for disease limited to the mucosa, and a dismal 10% 5-year survival for more advanced disease. The identification of factors involved in the pathogenesis and progression of biliary tract carcinoma is critical for devising effective methods of screening and treatment. Recent evidence suggests that reduction of the length of telomeres, which normally help maintain chromosomal stability, may promote the development and progression of a variety of carcinomas. Using a novel, recently validated telomere fluorescence in situ hybridization method, we examined telomere length in normal and inflamed gallbladder epithelium, metaplasia and dysplasia of the gallbladder, and biliary tract carcinoma to determine whether telomere shortening is associated with neoplastic progression in the biliary tract. Although normal and inflamed gallbladder epithelium demonstrated uniform normal telomere lengths, over half of all metaplastic lesions demonstrated shortened telomeres, supporting prior evidence that metaplastic lesions of the gallbladder are pre-neoplastic. Dysplastic epithelium and invasive carcinomas demonstrated almost universally abnormally short telomeres, indicating that telomere shortening occurs at an early, preinvasive stage of cancer development. In addition, invasive adenocarcinoma of the biliary tract frequently demonstrated intratumoral heterogeneity of telomere lengths. We conclude that telomere shortening is a consistent and early finding in the development of biliary tract carcinoma.


Crosslinking of lectins and receptors in membranes with hetero-bifunctional crosslinking reagents.
125I-Con A was reacted with the imidoester group of methyl 4-azidobenzoimidate and isolated from excess reagents on a Sephadex G-25 column. The hetero-bifunctional crosslinking reagent has two dissimilar functional groups, imidoester and arylazide, instead of two identical functional groups found in conventional homo-bifunctional crosslinking reagents. The two functional groups react under different conditions and it is possible to react one first and to activate the other later. Here the reagents were attached to the lectins by the imidoester reactions, and the arylazides now attached to the lectins were intended for the later use to crosslink the lectins and receptors. Human erythrocyte ghosts were incubated with the activated lectins, unbound lectins removed, and irradiated with UV to photolyze arylazides, thus crosslinking the lectins to the receptors in membranes. Upon the solubilization and subsequent electrophoresis of the sample, a new band appeared on the gel. 125I-Con A was detected in band A, the new band, and band 3, one of the membrane glycoproteins, diminished in parallel to the appearance of band A. The concurrent appearance of band A accompanied by 125I-Con A and decrease of band 3 were significantly reduced, when ghosts were incubated with the activated lectins but were not irradiated, ghosts were incubated with nonactivated 125I-Con A and irradiated, or ghosts were incubated with the activated concanavalin A in the presence of alpha-methylmannoside, the lectin inhibitor, and irradiated. The inhibitor removed a significant amount of the activated lectins bound to membranes, but failed to do so the activated lectins crosslinked into band A.


Pilot study of treatment with whole body hypothermia for neonatal encephalopathy.
There is extensive experimental evidence to support the investigation of treatment with mild hypothermia after birth asphyxia. However, clinical studies have been delayed by the difficulty in predicting long-term outcome very soon after birth and by concern about adverse effects of hypothermia. The objectives of this study were to determine whether it is feasible to select infants with a bad neurological prognosis and to begin hypothermic therapy within 6 hours of birth, and to observe the effect of this therapy on relevant physiologic variables. Sixteen newborn infants with clinical features of birth asphyxia (median cord blood pH: 6.74; range: 6.58-7.08) were assessed by amplitude integrated electroencephalography (aEEG), and mild whole body hypothermia was instituted within 6 hours of birth in the 10 infants with an aEEG prognostic of a bad outcome. Rectal temperature was maintained at 33.2 +/- (standard deviation).6 degrees C for 48 hours. Rectal and tympanic membrane temperature, blood pressure, heart rate, blood gases, blood lactate, full blood count, blood electrolytes, high and low shear rate viscosity, and coagulation studies were monitored during and after cooling. A preliminary assessment of neurological outcome was made by repeated magnetic resonance imaging (MRI) and neurological examination. All infants selected to receive hypothermia developed convulsions and a severe encephalopathy. During 48 hours of hypothermia infants had prolonged metabolic acidosis (median pH: 7.30; base excess: -6.3 mmol x L(-1), a high blood lactate (median lactate: 5.3 mmol x L(-1)) and low blood potassium levels (median value: 3.9 mmol x L(-1)) x Hypothermia was associated with lower heart rate and higher mean blood pressure. However, these changes did not seem to be clinically relevant and no significant complication of hypothermia was encountered. Blood viscosity and coagulation studies were similar during and after cooling. Unusual MRI findings were noted in 3 infants: transverse sinus thrombosis with subsequent small cerebellar infarct; probable thrombosis in the straight sinus; and hemorrhagic cerebral infarction. Six of the 10 cooled infants had minor abnormalities only or normal follow-up neurological examination; 3 infants died and 1 had major abnormalities. None of the 6 infants with a normal aEEG developed severe neonatal encephalopathy or neurological sequel. After birth asphyxia infants can be objectively selected by aEEG and hypothermia started within 6 hours of birth in infants at high risk of developing severe neonatal encephalopathy. Prolonged mild hypothermia to 33 degrees C to 34 degrees C is associated with minor physiologic abnormalities. Further studies of both the safety and efficacy of mild hypothermia, including further neuroimaging studies, are warranted.


Proved and potential vectors of yellow fever in South Africa.
This paper, based on records obtained from the Entomology Department of the South African Institute for Medical Research, Johannesburg, gives a summary of the distribution, adult habits, and breeding-places of the proved and potential vectors of yellow fever in South Africa.


Nomegestrol acetate ameliorated adipose atrophy in a rat model of cisplatin‑induced cachexia.
Cachexia, a complex disorder that results in depletion of adipose tissue and skeletal muscle, is driven by anorexia, metabolic abnormalities and inflammation. There are limited therapeutic options for this syndrome. Previous evidence has demonstrated that increasing adipose tissue may improve quality of life and survival outcomes in cachexia. Cisplatin, as a chemotherapy drug, also causes cachexia during antitumor therapy due to its adverse effects. To establish a rat model of cachexia, the animals were intraperitoneally treated with cisplatin at doses of 1, 2 and 3 mg/kg, and the rats that responded to cisplatin at the optimal dose were used to test the effect of nomegestrol acetate (NOMAc). Rats that were assessed to be sensitive to cisplatin were randomly grouped and intragastrically administered vehicle, 5 or 10 mg/kg megestrol acetate (MA) or 2.5, 5 or 10 mg/kg NOMAc. The body weights and food consumption of the rats were assessed. Serum IL-6 and TNF-α levels were assessed using ELISA. The protein expression levels of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), peroxisome proliferator activated receptor γ (PPARγ), fatty acid synthase (FASN) and sterol regulatory element-binding protein-1 (SREBP-1) from inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) were evaluated using western blotting. The optimal way to establish a chemotherapy-induced rat model of cachexia demonstrated in the present study was to intraperitoneally administer the rats with 2 mg/kg cisplatin for 3 consecutive days. NOMAc (2.5, 5 mg/kg) and MA (10 mg/kg) were able to significantly ameliorate the loss of body weight in the cisplatin-induced cachectic rats. NOMAc significantly reduced the serum levels of TNF-α at 10 mg/kg. Morphologically, iWAT atrophy, with a remarkable reduction in adipocyte volume, was observed in the cisplatin-induced cachectic rats, but the effects were reversed by administering 5, 10 mg/kg NOMAc or 10 mg/kg MA. Furthermore, 2.5 mg/kg NOMAc markedly reduced the protein expression levels of the lipolysis genes HSL and ATGL, and 5 mg/kg NOMAc markedly enhanced the protein expression levels of adipogenesis genes, including FASN, SREBP-1 and PPARγ in iWAT but not in eWAT. NOMAc was demonstrated to improve cachexia at lower doses compared with MA. Overall, NOMAc is likely to be a promising candidate drug for ameliorating cancer cachexia induced by cisplatin.


Disclosing donation decisions: the role of organ donor prototypes in an extended theory of planned behaviour.
This study explored the role of donor prototype evaluations (perceptions of the typical organ donor) in organ donation communication decisions using an extended theory of planned behaviour (TPB) model. The model incorporated attitude, subjective norm, perceived behavioural control, moral norm, self-identity, and donor prototype evaluations to predict intentions to record consent on an organ donor register and discuss the organ donation decision with significant others. Participants completed surveys assessing the extended TPB constructs related to registering (n = 359) and discussing (n = 282). Results supported a role for donor prototype evaluations in predicting discussing intentions only. Both extended TPB structural equation models were a good fit to the data, accounting for 74 and 76% of the variance in registering and discussing intentions, respectively. Participants' self-reported discussing behaviour (but not registering behaviour given low numbers of behavioural performers) was assessed 4 weeks later, with discussing intention as the only significant predictor of behaviour (Nagelkerke R(2) = 0.11). These findings highlight the impact of people's perceptions of a typical donor on their decisions to discuss their organ donation preference, assisting our understanding of the factors influencing individuals' communication processes in efforts to bridge the gap between organ supply and demand.


Evaluation of Intensity Modulated Radiation Therapy Delivery System using a Volumetric Phantom on the Basis of the Task Group 119 Report of American Association of Physicists in Medicine.
The current work describes the implementation of the American Association of Physicists in Medicine (AAPM)'s Task Group 119 report on a volumetric phantom (Delta4, Scandidos, Uppsala, Sweden) following the stated dose goals, to evaluate the step-and-shoot intensity modulated radiation therapy (IMRT) system. Delta4 consists of diode detectors, lying on two crossed planes, measuring the delivered dose, and providing two-dimensional dosimetric information. Seven plans of different goals and complexity were performed, with individual structure sets. TG199 structure sets and plans were transferred and implemented on the Delta4 phantom taking into account its cylindrical geometry. All plans were delivered with a 6 MV linear accelerator equipped with multileaf collimator of 1 cm thickness. Plan results for each test met the recommended dose goals. The evaluation was performed in terms of dose deviation, distance to agreement, and gamma index passing rate. In all test cases, the gamma index passing rate was measured >90%. Delta4 phantom has proven to be fast, applicable, and reliable for the step-and-shoot IMRT commissioning following TG119's recommended tests. Although AAPM's TG119 report is referring to the implementation of test plans that do not correspond to patient plans, it could be used as an evaluation tool of various IMRT systems, considering the local treatment planning system and the delivery system.


Cerebral atherosclerosis is associated with cystic infarcts and microinfarcts but not Alzheimer pathologic changes.
Some studies have reported associations between intracranial atherosclerosis and Alzheimer disease pathology. We aimed to correlate severity of cerebral atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy with neurofibrillary tangles, neuritic plaques, and cerebral infarcts. This autopsy study (n=163) was drawn from a longitudinal study of subcortical ischemic vascular disease, Alzheimer disease, and normal aging. Multivariable logistic regression models were used to test associations among the 3 forms of cerebrovascular disease and the presence of ischemic and neurodegenerative brain lesions. Apolipoprotein E genotype was included as a covariate in these multivariable models. Cerebral atherosclerosis was positively associated with microinfarcts (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2-4.4) and cystic infarcts (OR, 2.0; 95% CI, 1.0-4.2) but not Alzheimer disease pathology. Arteriolosclerosis showed a positive correlation with lacunar infarcts (OR, 2.0; 95% CI, 1.0-4.2) but not Alzheimer disease pathology. Cerebral amyloid angiopathy was inversely associated with lacunar infarcts (OR, 0.6; 95% CI, 0.41-1.1), but positively associated with Braak and Braak stage (OR, 1.5; 95% CI, 1.1-2.1) and Consortium to Establish a Registry for Alzheimer Disease plaque score (OR, 1.5; 95% CI, 1.1-2.2). Microinfarcts, which have been correlated with severity of cognitive impairment, were most strongly associated with atherosclerosis. Possible pathogenetic mechanisms include artery-to-artery emboli, especially microemboli that may include atheroemboli or platelet-fibrin emboli. Arteriolosclerosis was positively, whereas cerebral amyloid angiopathy was negatively correlated with lacunar infarcts, which might prove helpful in clinical differentiation of arteriolosclerotic from cerebral amyloid angiopathy-related vascular brain injury.


Comparison of the efficacies of two different fiber post-removal systems: A micro-computed tomography study.
The aim of this in vitro study was to compare the efficacies of two different fiber post-removal systems. Thirty extracted single-rooted mandibular premolar teeth were used. After RelyX fiber posts were cemented, the teeth were divided into two groups with regard to the post removal techniques: ultrasonic vibration and D.T. Light-Post removal kit. Residual material, tooth volume changes, working time and micro-crack formation were assessed using micro-computed tomography. All data were analyzed using Wilcoxon signed-rank and Mann-Whitney U tests. There was significantly more tooth root volume change in the ultrasonic group than removal kit group (p < .05). Fiber post removal time for the ultrasonic group was significantly longer than the removal kit group (p < .01).


Obstetric and Newborn Weak D-Phenotype RBC Testing and Rh Immune Globulin Management Recommendations: Lessons From a Blinded Specimen-Testing Survey of 81 Transfusion Services.
Modern RHD genotyping can be used to determine when patients with serologic weak D phenotypes have RHD gene variants at risk for anti-D alloimmunization. However, serologic testing, RhD interpretations, and laboratory management of these patients are quite variable. To obtain interlaboratory comparisons of serologic testing, RhD interpretations, Rh immune globulin (RhIG) management, fetomaternal hemorrhage testing, and RHD genotyping for weak D-reactive specimens. We devised an educational exercise in which 81 transfusion services supporting obstetrics performed tube-method RhD typing on 2 unknown red blood cell challenge specimens identified as (1) maternal and (2) newborn. Both specimens were from the same weak D-reactive donor. The exercise revealed how participants responded to these different clinical situations. Of reporting laboratories, 14% (11 of 80) obtained discrepant immediate-spin reactions on the 2 specimens. Nine different reporting terms were used to interpret weak D-reactive maternal RhD types to obstetricians. In laboratories obtaining negative maternal immediate-spin reactions, 28% (16 of 57) performed unwarranted antiglobulin testing, sometimes leading to recommendations against giving RhIG. To screen for excess fetomaternal hemorrhage after a weak D-reactive newborn, 47% (34 of 73) of reporting laboratories would have employed a contraindicated fetal rosette test, risking false-negative results and inadequate RhIG coverage. Sixty percent (44 of 73) of laboratories would obtain RHD genotyping in some or all cases. For obstetric and neonatal patients with serologic weak D phenotypes, we found several critical problems in transfusion service laboratory practices. We provide recommendations for appropriate testing, consistent immunohematologic terminology, and RHD genotype-guided management of Rh immune globulin therapy and RBC transfusions.


Induction of cyclooxygenase-1 and -2 modulates angiogenic responses to engagement of alphavbeta3.
Prostaglandins and cyclooxygenase (COX) have been implicated in the angiogenesis that occurs around tumours, but how they are induced is unclear. Prostaglandin formation is regulated by the availability of arachidonic acid and/or COX activity that in turn are controlled by activation of G-protein-coupled receptors or kinase receptors. Adhesion receptors provide another potential level of control as they transduce a variety of "outside-in" signals implicated in inflammation. We examined whether engagement of the vitronectin receptor (alphavbeta3) modulated prostacyclin (PGI2) formation in human umbilical vein endothelial cells (EC). Engagement of EC alphavbeta3 by vitronectin (versus fibronectin or gelatin) or by monoclonal antibodies (mAbs) LM609 and LIBS6, enhanced PGI2 generation and also induced expression of both COX-1 and -2 isoforms. Alphavbeta3 engagement also led to vascular endothelial cell growth factor (VEGF) generation and EC proliferation that was attenuated by inhibition of both COX-1 and COX-2. COX-1 inhibition also prevented new vessel formation in an in vitro model of angiogenesis that is alphavbeta3 dependent. Inhibition of angiogenesis by the COX-1 inhibitor was partially reversed by removal of the inhibitor or by addition of the stable analogue of PGI2, iloprost. These findings strongly indicate that alphavbeta3-mediated angiogenesis is partly due to induction of both isoforms of COX.


Sequence analysis of the whole genomes of five African human G9 rotavirus strains.
The G9 rotaviruses are amongst the most common global rotavirus strains causing severe childhood diarrhoea. However, the whole genomes of only a few G9 rotaviruses have been fully sequenced and characterised of which only one G9P[6] and one G9P[8] are from Africa. We determined the consensus sequence of the whole genomes of five African human group A G9 rotavirus strains, four G9P[8] strains and one G9P[6] strain collected in Cameroon (central Africa), Kenya (eastern Africa), South Africa and Zimbabwe (southern Africa) in 1999, 2009 and 2010. Strain RVA/Human-wt/ZWE/MRC-DPRU1723/2009/G9P[8] from Zimbabwe, RVA/Human-wt/ZAF/MRC-DPRU4677/2010/G9P[8] from South Africa, RVA/Human-wt/CMR/1424/2009/G9P[8] from Cameroon and RVA/Human-wt/KEN/MRC-DPRU2427/2010/G9P[8] from Kenya were on a Wa-like genetic backbone and were genotyped as G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. Strain RVA/Human-wt/ZAF/MRC-DPRU9317/1999/G9P[6] from South Africa was genotyped as G9-P[6]-I2-R2-C2-M2-A2-N1-T2-E2-H2. Rotavirus A strain MRC-DPRU9317 is the second G9 strain to be reported on a DS-1-like genetic backbone, the other being RVA/Human-wt/ZAF/GR10924/1999/G9P[6]. MRC-DPRU9317 was found to be a reassortant between DS-1-like (I2, R2, C2, M2, A2, T2, E2 and H2) and Wa-like (N1) genome segments. All the genome segments of the five strains grouped strictly according to their genotype Wa- or DS-1-like clusters. Within their respective genotypes, the genome segments of the three G9 study strains from southern Africa clustered most closely with rotaviruses from the same geographical origin and with those with the same G and P types. The highest nucleotide identity of genome segments of the study strains from eastern and central Africa regions on a Wa-like backbone was not limited to rotaviruses with G9P[8] genotypes only, they were also closely related to G12P[6], G8P[8], G1P[8] and G11P[25] rotaviruses, indicating a close inter-genotype relationship between the G9 and other rotavirus genotypes. Rotavirus strain MRC-DPRU9317 is the first G9P[6] to be characterised on a DS-1-like genetic backbone with a reassortant segment 8 (NSP2) and fourth G9P[6] to be fully sequenced globally.


Tgfbr2 disruption in postnatal smooth muscle impairs aortic wall homeostasis.
TGF-β is essential for vascular development; however, excess TGF-β signaling promotes thoracic aortic aneurysm and dissection in multiple disorders, including Marfan syndrome. Since the pathology of TGF-β overactivity manifests primarily within the arterial media, it is widely assumed that suppression of TGF-β signaling in vascular smooth muscle cells will ameliorate aortic disease. We tested this hypothesis by conditional inactivation of Tgfbr2, which encodes the TGF-β type II receptor, in smooth muscle cells of postweanling mice. Surprisingly, the thoracic aorta rapidly thickened, dilated, and dissected in these animals. Tgfbr2 disruption predictably decreased canonical Smad signaling, but unexpectedly increased MAPK signaling. Type II receptor-independent effects of TGF-β and pathological responses by nonrecombined smooth muscle cells were excluded by serologic neutralization. Aortic disease was caused by a perturbed contractile apparatus in medial cells and growth factor production by adventitial cells, both of which resulted in maladaptive paracrine interactions between the vessel wall compartments. Treatment with rapamycin restored a quiescent smooth muscle phenotype and prevented dissection. Tgfbr2 disruption in smooth muscle cells also accelerated aneurysm growth in a murine model of Marfan syndrome. Our data indicate that basal TGF-β signaling in smooth muscle promotes postnatal aortic wall homeostasis and impedes disease progression.


Factors mediating the hemodynamic effects of tumor necrosis factor-alpha in portal hypertensive rats.
Nitric oxide, prostacyclin, and glucagon have been implicated in promoting the hyperdynamic circulatory state of portal hypertension. Recent evidence also indicates that increased tumor necrosis factor-alpha (TNF-alpha) production is involved in the pathogenesis of this hemodynamic abnormality. This study was aimed at investigating in rats with portal vein stenosis (PVS) the effects on splanchnic hemodynamics of blocking circulating TNF-alpha and the factors mediating the vascular action of this cytokine in this setting. Anti-TNF-alpha polyclonal antibodies or placebo was injected into rats (n = 96) before and 4 days after PVS (short-term inhibition) and at 24 h and 4, 7, 10 days after PVS (long-term inhibition). Short-term TNF-alpha inhibition reduced portal venous inflow and cardiac index and increased splanchnic and systemic resistance. Portal pressure was unchanged, but portal-systemic shunting was decreased. After long-term TNF-alpha inhibition, portal venous inflow and portal pressure were unchanged, but arterial pressure and systemic resistance rose significantly. Anti-TNF-alpha PVS rats exhibited lower increments of systemic resistance after Nomega-nitro-L-arginine methyl ester and indomethacin administration and lower serum levels of TNF-alpha, nitrates-nitrites, and 6-keto-PGF1alpha, both over the short and the long term. Serum glucagon levels rose after long-term inhibition. In conclusion, the specific role played by TNF-alpha in the development of the hyperdynamic state of portal hypertension appears to be mainly mediated through an increased release of nitric oxide and prostacyclin. Maintenance of the splanchnic hyperemia after long-term TNF-alpha inhibition could be due to a compensatory release of glucagon.


Correction for scatter in 3D brain PET using a dual energy window method.
A method for scatter correction using dual energy window acquisition has been developed and implemented on data collected with a brain-PET tomograph operated in the septa retracted, 3D mode. Coincidence events are assigned to (i) an upper energy window where both photons deposit energy between 380 keV and 850 keV or (ii) a lower energy window where one or both photons deposit within 200 keV and 380 keV. Scaling parameters are derived from measurements of the ratios of counts from line sources due to scattered and unscattered events in the two energy windows in head-sized phantoms. A scaled subtraction of the two energy windows produces a distribution of scatter which is smoothed prior to subtraction from the upper energy window. In phantoms, the correction was found to restore the uniformity, contrast and linearity of activity concentration. Relative activity concentrations were restored to within 7% of their true values in a multicompartment phantom. The method was found to provide accurate correction for scattered events arising from activity outside the direct detector field of view. In a three-compartment phantom containing water, 18F and 11C scanned in dynamic, multiframe mode, the half-lives of the two isotopes were restored to within 2% of their true value.


Effect of whole body resistance training on arterial compliance in young men.
The effect of resistance training on arterial stiffening is controversial. We tested the hypothesis that resistance training would not alter central arterial compliance. Young healthy men (age, 23 +/- 3.9 (mean +/- s.e.m.) years; n = 28,) were whole-body resistance trained five times a week for 12 weeks, using a rotating 3-day split-body routine. Resting brachial blood pressure (BP), carotid pulse pressure, carotid cross-sectional compliance (CSC), carotid initima-media thickness (IMT) and left ventricular dimensions were evaluated before beginning exercise (PRE), after 6 weeks of exercise (MID) and at the end of 12 weeks of exercise (POST). CSC was measured using the pressure-sonography method. Results indicate reductions in brachial (61.1 +/- 1.4 versus 57.6 +/- 1.2 mmHg; P < 0.01) and carotid pulse pressure (52.2 +/- 1.9 versus 46.8 +/- 2.0 mmHg; P < 0.01) PRE to POST. In contrast, carotid CSC, beta-stiffness index, IMT and cardiac dimensions were unchanged. In young men, central arterial compliance is unaltered with 12 weeks of resistance training and the mechanisms responsible for cardiac hypertrophy and reduced arterial compliance are either not inherent to all resistance-training programmes or may require a prolonged stimulus.


What is the prevalence of clinically significant endoscopic findings in subjects with dyspepsia? Systematic review and meta-analysis.
Evolving definitions of dyspepsia may lead to differences in the prevalence of clinically significant findings encountered at upper gastrointestinal (GI) endoscopy in sufferers. However, few studies report the prevalence of endoscopic findings in individuals with dyspepsia. We conducted a systematic review and meta-analysis examining this. MEDLINE and EMBASE were searched through April 2010 to identify relevant articles (23,457 citations). Eligible studies recruited adults from the community, workplace, blood donation or screening clinics, family physician offices, or internal medicine clinics. Studies were required to report prevalence of dyspepsia and perform upper gastrointestinal endoscopy in a proportion of, or all, participants. Prevalence of clinically significant endoscopic findings in subjects with and without dyspepsia was pooled for all studies, and compared using odds ratios and 95% confidence intervals. Of 240 papers evaluated, 151 reported prevalence of dyspepsia. Nine reported prevalence of endoscopic findings among 5389 participants. Erosive esophagitis was the most common abnormality encountered (pooled prevalence 13.4%) followed by peptic ulcer (pooled prevalence 8.0%). The only finding encountered more frequently in individuals with dyspepsia, compared with those without, was peptic ulcer (odds ratio, 2.07; 95% confidence interval, 1.52-2.82). Prevalence of erosive esophagitis was lower when the Rome criteria were used to define dyspepsia compared with a broad definition (6% vs 20%). Erosive esophagitis was the most common finding encountered at endoscopy for dyspepsia, though prevalence was lower when the Rome criteria were used to define dyspepsia. Only peptic ulcer was more common in individuals with dyspepsia.


Management of upper respiratory tract infections in children.
Upper respiratory tract infection (URTI) occurs commonly in both children and adults and is a major cause of mild morbidity. It has a high cost to society, being responsible for absenteeism from school and work and unnecessary medical care, and is occasionally associated with serious sequelae. URTIs are usually caused by several families of virus; these are the rhinovirus, coronavirus, parainfluenza, respiratory syncytial virus (RSV), adenovirus, human metapneumovirus, influenza, enterovirus and the recently discovered bocavirus. This review will mainly focus on the rhinovirus, where significant advances have been made in understanding the epidemiology, natural history and relationship with other pathogens.


Risk adjustment for a children's capitation rate.
Few capitation arrangements vary premiums by a child's health characteristics, yielding an incentive to discriminate against children with predictably high expenditures from chronic diseases. In this article, we explore risk adjusters for the 35 percent of the variance in annual out-patient expenditure we find to be potentially predictable. Demographic factors such as age and gender only explain 5 percent of such variance; health status measures explain 25 percent, prior use and health status measures together explain 65 to 70 percent. The profit from risk selection falls less than proportionately with improved ability to adjust for risk. Partial capitation rates may be necessary to mitigate skimming and dumping.


CIP2A expression predicts recurrences of tamoxifen-treated breast cancer.
CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours and generally correlated with higher tumour grade and therapeutic resistance. CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A, stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although further biological mechanisms for CIP2A are yet to be defined. CIP2A protein expression was studied by immunohistochemistry in oestrogen receptor-positive primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total, 51 cases presented with a relapse or metastasis during adjuvant treatment with tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored separately for cytoplasmic, nuclear, or membranous staining, and scores were tested for statistically significant relationships with clinicopathological features. Membranous CIP2A was preferentially expressed in cases who experienced a recurrence during tamoxifen treatment thus predicting a worse overall survival (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p < 0.001). Cox multivariate analysis indicates that it is an independent prognostic indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the assessment of membranous CIP2A expression as a potential novel prognostic and predictive indicator for tamoxifen resistance and recurrence within oestrogen receptor-positive breast cancer.


Restoration of gap junctions in the regenerative process of ethanol-induced gastric mucosal injury.
Gap junctions mediate intercellular communication and play an important role in cell proliferation and differentiation. The present study examined the expression of the gap junction protein connexin 32 in rat gastric mucosa during the regenerative process of ethanol-induced gastric mucosal injury. Absolute ethanol (0.5 mL/100 g bodyweight) was administered to rats via gastric intubation. Following the treatment, rats were killed periodically, and gastric tissues were processed for indirect immunofluorescence microscopy using an anti-connexin 32 antibody. Haematoxylin and eosin (H&E), periodic acid Schiff (PAS) and Bromodeoxyuridine (BrdU) staining were also performed in serial sections. Gastric injuries were limited in the mucosal layer. The injury was most severe 1 h after treatment, and was completely resolved by the 4th day after treatment. The number of immunoreactive spots for gap junctions was markedly decreased 1 h after the ethanol treatment. Reappearance of these immunostaining gap junctions occurred with repair of the injury. The reappearance of connexin 32 after injury was delayed in comparison with both the histologic resolution of the injury and the normalization of PAS-stained mucus. In contrast, the time course of reappearance of gap junctions closely paralleled the appearance of BrdU-labelled cells. These results indicate that morphologic repair is different to the recovery of cell maturity and cell proliferation in the regenerative gastric mucosa.


Adaptive resolution min-max classifiers.
A high automation degree is one of the most important features of data driven modeling tools and it should be taken into consideration in classification systems design. In this regard, constructive training algorithms are essential to improve the automation degree of a modeling system. Among neuro-fuzzy classifiers, Simpson's (1992) min-max networks have the advantage of being trained in a constructive way. The use of the hyperbox, as a frame on which different membership functions can be tailored, makes the min-max model a flexible tool. However, the original training algorithm evidences some serious drawbacks, together with a low automation degree. In order to overcome these inconveniences, in this paper two new learning algorithms for fuzzy min-max neural classifiers are proposed: the adaptive resolution classifier (ARC) and its pruning version (PARC). ARC/PARC generates a regularized min-max network by a succession of hyperbox cuts. The generalization capability of ARC/PARC technique mostly depends on the adopted cutting strategy. By using a recursive cutting procedure (R-ARC and R-PARC) it is possible to obtain better results. ARC, PARC, R-ARC, and R-PARC are characterized by a high automation degree and allow to achieve networks with a remarkable generalization capability. Their performances are evaluated through a set of toy problems and real data benchmarks. The paper also proposes a suitable index that can be used for the sensitivity analysis of the classification systems under consideration.


Collagen secretion screening in Drosophila supports a common secretory machinery and multiple Rab requirements.
Collagens are large secreted trimeric proteins making up most of the animal extracellular matrix. Secretion of collagen has been a focus of interest for cell biologists in recent years because collagen trimers are too large and rigid to fit into the COPII vesicles mediating transport from the endoplasmic reticulum (ER) to the Golgi. Collagen-specific mechanisms to create enlarged ER-to-Golgi transport carriers have been postulated, including cargo loading by conserved ER exit site (ERES) protein Tango1. Here, we report an RNAi screening for genes involved in collagen secretion in Drosophila. In this screening, we examined distribution of GFP-tagged Collagen IV in live animals and found 88 gene hits for which the knockdown produced intracellular accumulation of Collagen IV in the fat body, the main source of matrix proteins in the larva. Among these hits, only two affected collagen secretion specifically: PH4αEFB and Plod, encoding enzymes known to mediate posttranslational modification of collagen in the ER. Every other intracellular accumulation hit affected general secretion, consistent with the notion that secretion of collagen does not use a specific mode of vesicular transport, but the general secretory pathway. Included in our hits are many known players in the eukaryotic secretory machinery, like COPII and COPI components, SNAREs and Rab-GTPase regulators. Our further analysis of the involvement of Rab-GTPases in secretion shows that Rab1, Rab2 and RabX3, are all required at ERES, each of them differentially affecting ERES morphology. Abolishing activity of all three by Rep knockdown, in contrast, led to uncoupling of ERES and Golgi. We additionally present a characterization of a screening hit we named trabuco (tbc), encoding an ERES-localized TBC domain-containing Rab-GAP. Finally, we discuss the success of our screening in identifying secretory pathway genes in comparison to two previous secretion screenings in Drosophila S2 cells.


Towards a spectroscopic protocol for unambiguous detection of quantum coherence in excitonic energy transport.
The role of quantum effects in excitonic energy transport (EET) has been scrutinised intensely and with increasingly sophisticated experimental techniques. This increased complexity requires invoking correspondingly elaborate models to fit spectroscopic data before molecular parameters can be extracted. Possible quantum effects in EET can then be studied, but the conclusions are strongly contingent on the efficacy of the fitting and the accuracy of the model. To circumvent this challenge, we propose a witness for quantum coherence in EET that can be extracted directly from two-pulse pump-probe spectroscopy experimental data. We provide simulations to judge the feasibility of our approach. Somewhat counterintuitively, our protocol does not probe quantum coherence directly, but only indirectly through its implicit deletion. It allows for classical models with no quantum coherence to be decisively ruled out.


Increased bilateral expression of α1-adrenoceptors on peripheral nerves, blood vessels and keratinocytes does not account for pain or neuroinflammatory changes after distal tibia fracture in rats.
In certain forms of nerve injury and inflammation, noradrenaline augments pain via actions on up-regulated α1-adrenoceptors (α1-ARs). The aim of this study was to use immunohistochemistry to examine α1-AR expression on peripheral neurons, cutaneous blood vessels and keratinocytes after distal tibia fracture and cast immobilization, a model of complex regional pain syndrome type 1. We hypothesized that there would be increased α1-AR expression on neurons and keratinocytes in the injured limb in comparison to the contralateral unaffected limb after distal tibia fracture, in association with inflammatory changes and pain. α1-AR expression was increased on plantar keratinocytes, dermal blood vessels and peripheral nerve fibers at 16weeks after injury both in the fractured and contralateral uninjured limb. Similar changes were seen in controls whose limb had been immobilized in a cast for 4weeks but not fractured. Neurofilament 200 (NF200), a marker of myelinated neurons, and calcitonin gene-related peptide (CGRP), a neuropeptide involved in neuro-inflammatory signaling, decreased 4weeks after fracture and casting but then increased at the 16-week time point. As some of these changes were also detected in the contralateral hind limb, they probably were triggered by a systemic response to fracture and casting. Soon after the cast was removed, intraplantar injections of the α1-AR antagonist prazosin released local vasoconstrictor tone but had no effect on pain behaviors. However, systemic injection of prazosin inhibited behavioral signs of pain, suggesting that fracture and/or casting triggered an up-regulation of α1-ARs in central nociceptive pathways that augmented pain. Together, these findings indicate that α1-AR expression increases in the hind limbs after distal tibia fracture and cast immobilization. However, these peripheral increases do not contribute directly to residual pain.


Modulation of membrane curvature by peptides.
The fusion of two stable bilayers likely proceeds through intermediates in which the membrane acquires curvature. The insertion of peptides into the membrane will affect its curvature tendency. Studies with a number of small viral fusion peptides indicate that these peptides promote negative curvature at low concentration. This is in accord with the curvature requirements to initiate membrane fusion according to the stalk-pore model. Although a characteristic of fusion peptides, the promotion of negative curvature is only one of several mechanisms by which fusion proteins accelerate the rate of fusion. In addition, the fusion peptide itself, as well as other regions in the viral fusion protein, facilitates membrane fusion by mechanisms that are largely independent of curvature. Leakage of the internal aqueous contents of liposomes is another manifestation of the alteration of membrane properties. Peptides exhibit quite different relative potencies between fusion and leakage that is determined by the structure and mode of insertion of the peptide into the membrane.


Immunohistochemical localization of epidermal growth factor-like activity in the hamster ovary with a polyclonal antibody.
A polyclonal antibody to murine epidermal growth factor (EGF) was generated in rabbits and characterized by RIA, Western blots, and dot blotting. The antibody detected as little as 0.01 ng of mouse EGF in dot blots at 1:100,000 dilution and 5 pg of EGF in RIA at 1:50,000 dilution; it did not cross-react with transforming growth factor-alpha, insulin-like growth factor, or fibroblast growth factor. Ovarian EGF content peaked (17 +/- 2 pg/nonluteal ovary) on Day 1 (estrus as determined by copious vaginal discharge) and declined by DAy 3 as measured by RIA of immunoaffinity-purified ovarian extract. Frozen sections of hamster ovaries were stained immunohistochemically for EGF using a Zymed kit. Intense red staining specific for EGF was localized only in granulosa cells of small (1-2 layers of granulosa cells) and medium (3-6 layers of granulosa cells) preantral follicles; moderate staining was observed in the granulosa and theca cells of small antral follicles. Staining intensity faded in granulosa and theca cells of large antral follicles, especially on Day 4 (proestrus) and disappeared in pyknotic granulosa cells of atretic follicles. Follicular EGF staining peaked on Days 1 and 2 and thereafter declined to low levels. On Day 2, oocytes of the primordial follicles showed distinct coloration. Sections of Day 2 ovary incubated with preneutralized antibody or normal rabbit IgG did not show any coloration. For intact hamsters, 10 micrograms of follicle-stimulating hormone (FSH), twice daily for Days 1 and 2, intensified EGF staining in granulosa cells compared with corresponding untreated Day 3 hamsters, whereas similar treatment with luteinizing hormone for 2 days expanded the interstitium with localized staining of interstitial cells only around follicles with 2 and 3 layers of granulosa cells and lacking theca. Hypophysectomy for 13 days resulted in almost complete absence of EGF-specific staining in the remaining nonatretic follicles; however, exogenous FSH (5 micrograms, twice daily) for 2 days dramatically increased staining intensity associated with newly developed follicles. Luteinizing hormone (0.4 micrograms, twice daily) for 2 days, however, induced significant development of only the interstitium with increased staining of small preantral follicles. These results provide strong evidence for the presence of EGF-like activity in hamster ovarian follicles and suggest that its expression is controlled by gonadotropins, especially FSH.


Community contributions to a FHU team work.
Considering the importance of people participating in the construction of new health models, this study aimed to characterize and analyze contributions brought by community to health actions carried out in a Family Health Unit. It is a documentary analysis based on the records of 24 monthly meetings between the team and community. After reading the records, subject was divided into four themes: material and human resources, availability to secondary level health services, community adherence to the unit activities, health promotion and disease prevention. Discussions opened a wide perspective on health and stimulated co-responsibility, stronger links and information exchanging. Nevertheless, there is a need to improve community effective participation in the co-management of the health system.


Altered pathways for auditory discrimination and recognition memory in preterm infants.
Preterm infants are at increased risk for cognitive disorders, including impairments in recognition memory. This study evaluated the effects of extreme prematurity on the neural pathway for auditory recognition memory using event-related potentials (ERPs), a neurophysiological technique widely used in cognitive neuroscience. ERPs were recorded at term postmenstrual age in 35 preterm infants born at less than 32 weeks' gestation (22 males, 13 females; mean birthweight ([BW] 1154g, SD 374g) with normal brain ultrasounds, compared with 40 healthy, term newborns (1 to 3 days of age; 20 males, 20 females; BW 3672g, SD 420g). Because infants must be able to detect and discriminate sounds before recognizing them, two paradigms were used to assess these functions. The first evaluated the detection and discrimination of speech sounds. The second tested recognition of the mother's voice compared with a stranger's. Results showed significantly different patterns of speech sound discrimination in preterm infants compared with term infants. No evidence of maternal voice recognition was elicited from the preterm infants. No specific patterns of auditory detection or discrimination were associated with patterns of recognition memory, suggesting that the function of multiple neural pathways may have been altered in this group of preterm infants. These results provide a functional corroboration of magnetic resonance imaging studies showing effects of prematurity on early brain development, even among preterm infants with normal cranial ultrasonography.


Polysomnography versus limited respiratory monitoring and nurse-led titration to optimise non-invasive ventilation set-up: a pilot randomised clinical trial.
Polysomnography (PSG) is recommended for non-invasive ventilation (NIV) set-up in patients with chronic respiratory failure. In this pilot randomised clinical trial, we compared the physiological effectiveness of NIV set-up guided by PSG to limited respiratory monitoring (LRM) and nurse-led titration in patients with COPD-obstructive sleep apnoea (OSA) overlap. The principal outcome of interest was change in daytime arterial partial pressure of carbon dioxide (PaCO2) at 3 months. Fourteen patients with daytime PaCO2 >6 kPa and body mass index >30 kg/m2 were recruited. At 3 months, PaCO2 was reduced by -0.88 kPa (95% CI -1.52 to -0.24 kPa) in the LRM group and by -0.36 kPa (95% CI -0.96 to 0.24 kPa) in the PSG group. These pilot data provide support to undertake a clinical trial investigating the clinical effectiveness of attended limited respiratory monitoring and PSG to establish NIV in patients with COPD-OSA overlap. TRIAL NUMBER: Results, NCT02444806.


Simulation tools for particle-based reaction-diffusion dynamics in continuous space.
Particle-based reaction-diffusion algorithms facilitate the modeling of the diffusional motion of individual molecules and the reactions between them in cellular environments. A physically realistic model, depending on the system at hand and the questions asked, would require different levels of modeling detail such as particle diffusion, geometrical confinement, particle volume exclusion or particle-particle interaction potentials. Higher levels of detail usually correspond to increased number of parameters and higher computational cost. Certain systems however, require these investments to be modeled adequately. Here we present a review on the current field of particle-based reaction-diffusion software packages operating on continuous space. Four nested levels of modeling detail are identified that capture incrementing amount of detail. Their applicability to different biological questions is discussed, arching from straight diffusion simulations to sophisticated and expensive models that bridge towards coarse grained molecular dynamics.


A comparison of the local and remote effects of basement-membrane regeneration in normal and diabetic rats.
If the capsule basement membrane of the lens is partially removed, the underlying epithelial cells of the normal rat, as the animal ages, continue to produce basement membrane as if the membrane had not been disturbed. The response of the diabetic animal is quite different and basement membrane synthesis is increased by about 60%. Furthermore, this increase also occurs although at a reduced rate in the opposite eye where basement membrane was undisturbed. This might be termed a "sympathetic effect" and appears to be due to a substance or substances dissolved in the aqueous humour of the sympathizing eye and arising from increased activity of cells producing basement membrane in the other eye.


Telephone Problem Solving for Service Members with Mild Traumatic Brain Injury: A Randomized, Clinical Trial.
Mild traumatic brain injury (mTBI) is a common injury for service members in recent military conflicts. There is insufficient evidence of how best to treat the consequences of mTBI. In a randomized, clinical trial, we evaluated the efficacy of telephone-delivered problem-solving treatment (PST) on psychological and physical symptoms in 356 post-deployment active duty service members from Joint Base Lewis McChord, Washington, and Fort Bragg, North Carolina. Members with medically confirmed mTBI sustained during deployment to Iraq and Afghanistan within the previous 24 months received PST or education-only (EO) interventions. The PST group received up to 12 biweekly telephone calls from a counselor for subject-selected problems. Both groups received 12 educational brochures describing common mTBI and post-deployment problems, with follow-up for all at 6 months (end of PST), and at 12 months. At 6 months, the PST group significantly improved on a measure of psychological distress (Brief Symptom Inventory; BSI-18) compared to the EO group (p = 0.005), but not on post-concussion symptoms (Rivermead Post-Concussion Symptoms Questionnaire [RPQ]; p = 0.19), the two primary endpoints. However, these effects did not persist at 12-month follow-up (BSI, p = 0.54; RPQ, p = 0.45). The PST group also had significant short-term improvement on secondary endpoints, including sleep (p = 0.01), depression (p = 0.03), post-traumatic stress disorder (p = 0.04), and physical functioning (p = 0.03). Participants preferred PST over EO (p < 0.001). Telephone-delivered PST appears to be a well-accepted treatment that offers promise for reducing psychological distress after combat-related mTBI and could be a useful adjunct treatment post-mTBI. Further studies are required to determine how to sustain its effects. (Trial registration: ClinicalTrials.gov Identifier: NCT01387490 https://clinicaltrials.gov ).


The role of self-efficacy, coping, and lapses in weight maintenance.
Successful weight maintenance after weight loss is exceedingly rare. The present study aimed to identify psychological predictors of lapses and weight maintenance. Self-efficacy, coping, and perceptions of lapses were examined as potential predictors of lapse frequency and weight maintenance (percentage weight loss maintained). Participants included 67 adults (85.3 % women) who had intentionally lost a mean of 16 % of their body weight and had stopped losing weight at least 6 months prior to data collection. Participants completed a 7-day lapse diary tracking the frequency and perceived severity of their dietary and activity lapses, along with questionnaires on self-efficacy, coping, and characteristics of their weight loss. Participants had lost a mean of 13.9 kg, 20.4 months prior to data collection. More frequent lapsing was correlated with lower self-efficacy and greater perceived lapse severity. Lower percentage of weight loss maintained was correlated with lower self-efficacy, poorer coping, greater perceived lapse severity, and longer time since weight loss ended. "Regainers," who maintained <90 % of their weight loss, had poorer self-efficacy, poorer coping, greater lapse frequency, and greater perceived lapse severity, than "maintainers," who maintained at least 90 % of their weight loss. The results suggest that self-efficacy, coping, and perceived lapse severity are significant predictors of weight maintenance, consistent with the relapse prevention model. The goals of improving self-efficacy and coping skills might be important additions to weight maintenance programs.


The role of chloride transport in postsynaptic inhibition of hippocampal neurons.
Hippocampal inhibitory postsynaptic potentials are depolarizing in granule cells but hyperpolarizing in CA3 neurons because the reversal potentials and membrane potentials of these cells differ. Here the hippocampal slice preparation was used to investigate the role of chloride transport in these inhibitory responses. In both cell types, increasing the intracellular chloride concentration by injection shifted the reversal potential of these responses in a positive direction, and blocking the outward transport of chloride with furosemide slowed their recovery from the injection. In addition, hyperpolarizing and depolarizing inhibitory responses and the hyperpolarizing and depolarizing responses to the inhibitory neurotransmitter gamma-aminobutyric acid decreased in the presence of furosemide. These effects of furosemide suggest that the internal chloride activity of an individual hippocampal neuron is regulated by two transport processes, one that accumulates chloride and one that extrudes chloride.


Closing the Gender Gap in Fragile X Syndrome: Review on Females with FXS and Preliminary Research Findings.
Fragile X syndrome (FXS) is a genetic condition known to increase the risk of cognitive impairment and socio-emotional challenges in affected males and females. To date, the vast majority of research on FXS has predominantly targeted males, who usually exhibit greater cognitive impairment compared to females. Due to their typically milder phenotype, females may have more potential to attain a higher level of independence and quality of life than their male counterparts. However, the constellation of cognitive, behavioral, and, particularly, socio-emotional challenges present in many females with FXS often preclude them from achieving their full potential. It is, therefore, critical that more research specifically focuses on females with FXS to elucidate the role of genetic, environmental, and socio-emotional factors on outcome in this often-overlooked population.


[What scientific and clinical findings will result from the controlled trial "Women's Health Initiative"?].
The Women's Health Initiative Study is the first large randomized controlled trial for primary prevention, comparing the beneficial or adverse effects of an oral continuous-combined regimen of conjugated estrogens + medroxyprogesterone acetate, vs placebo in late postmenopausal women. This study brings evidence for an absence of preventive cardiovascular effects of hormone replacement therapy (HRT), shows for the first time a small increase in risk for coronary disease, and confirms a small increased risk for invasive breast cancer from four-five years of treatment on, a reduction of risk of colorectal cancer and osteoporotic fractures, and a moderate increase in other already known cardiovascular risks during HRT, such as venous thromboembolism and stroke. Although this study has inherent limitations and may be criticised, and the observed risks are restricted, it forces the physician to better respect known contra-indications (a.o. vascular) to HRT, to carefully weigh the benefit/risk balance of the patients, shorten HRT administration (4-5 years?), use minimal effective hormone dosages, preferably by non-oral route, and change for new compounds with more selective estrogenic action, which are under development.